Open AccessApelin-13 ameliorates LPS-induced BV-2 microglia inflammatory response through promoting autophagy and inhibiting H3K9ac enrichment of TNF-α and IL-6 promoter
Author(s) -
Qing-Ming Peng,
Jian Zhou,
Xu Zhang,
Qiancheng Zhao,
Zhi-Yue Li,
Qun Zhao
Publication year - 2022
Publication title -
acta neurobiologiae experimentalis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.542
H-Index - 55
eISSN - 1689-0035
pISSN - 0065-1400
DOI - 10.55782/ane-2022-006
Subject(s) - microglia , neuroinflammation , tumor necrosis factor alpha , western blot , apelin , histone deacetylase , chemistry , autophagy , inflammation , lipopolysaccharide , hdac1 , microbiology and biotechnology , cancer research , biology , endocrinology , immunology , histone , receptor , biochemistry , apoptosis , gene
Microglia is activated and polarized to pro‑inflammatory M1 phenotype or anti‑inflammatory M2 phenotype in neuroinflammation.Apelin‑13 exerts protective properties against neuroinflammation in several neurological disorders. We aimed to investigate whetherapelin‑13 played a protective role on BV‑2 microglia and explore its underlying mechanisms. Lipopolysaccharide (LPS)‑stimulatedBV‑2 microglia cells were treated with apelin‑13. Microglia activation was evaluated by immunofluorescence with F‑actin. Westernblot was performed to measure the expression of autophagy associated proteins. CD16/32 and CD206 were detected to assessmicroglia polarization by western blot and flow cytometry. qRT‑PCR was utilized to measure inducible nitric oxide synthase (iNOS),arginase‑1 (Arg‑1), interleukin‑10 (IL‑10), interleukin‑6 (IL‑6) and tumor necrosis factor‑alpha (TNF‑α). Histone H3 acetyl lysine 9(H3K9ac) enrichment of TNF‑α and IL‑6 promoter was detected by ChIP. We discovered that apelin‑13 impacted the actin cytoskeleton,recovering the control phenotype following LPS exposure. Apelin‑13 improved autophagy‑mediated microglia polarization towards M2phenotype to alleviate inflammatory response in LPS‑stimulated cells. Autophagy flux inhibitor chloroquine antagonized these effectsof apelin‑13 on LPS‑stimulated cells. Besides, apelin‑13 decreased the enrichment of H3K9ac at the promoter region of TNF‑α and IL‑6to inhibit inflammatory response, which was reversed by histone deacetylase antagonist valproate. Taken together, apelin‑13 alleviatedinflammation via facilitating microglia M2 polarization due to autophagy promotion, and inhibiting H3K9ac enrichment on promoterregions of TNF‑α and IL‑6.